Recent U.S. health statistics indicate that there are currently over 50 million individuals who have clinically diagnosed osteoarthritis, a joint disease that results from breakdown of joint cartilage and underlying bone. Furthermore, approximately 40% of this population is living with chronic joint pain. It is estimated that about 3% of the population between the ages of 40-65 (or nearly 2.8 million patients) suffers from and seeks medical treatment for hip osteoarthritis. Of these nearly 2.8 million patients, an estimated 840,000 (about 30%) suffer from activity limiting hip osteoarthritis, and it is typically these patients who are recommended for hip replacement surgery, also known as total hip arthroplasty.
Currently, it is estimated that approximately 15% of these 840,000 patients choose to undergo hip replacement surgery. This low percentage can be attributed to the relatively short projected lifetime of a hip implant for an active patient as well as the subsequent need for a revision surgery. Revision surgery, to modify a previously implanted hip implant, is associated with significant complications, co-morbidities, and overall decreased effectiveness.
Due to the lack of ideal solutions, many active patients between the ages of 40-65 are left to manage their pain through pharmaceuticals (e.g., Nonsteroidal anti-inflammatory drugs (NSAIDs)) or nutraceuticals (i.e., glucosamine and chondroitin sulfate). Thus, to address this population of active, young patients (40-65 years of age) who suffer from activity limiting hip osteoarthritis but who are not good candidates for total joint arthroplasty procedures, an approach is needed that targets the replacement of diseased cartilage (cartilage having large arthritic lesions) of the osteoarthritic, degenerated joint. Any treatment for this patient population that can stave off a traditional total hip arthroplasty procedure, provide pain relief, and restore an active lifestyle would solve a clinical problem for which no good solutions currently exist.
Many technologies have been introduced in an attempt to address this patient population. Some of these technologies include hemiarthroplasty, in which both sides of the hip joint are resurfaced or temporarily covered with metal prosthetic caps. Some implants used for hemiarthroplasty are “metal-on-metal,” wherein metal is applied to both sides of the hip joint. While metal-on-metal implants used in hemiarthroplasty demonstrate good early success, recent studies have documented high levels of failure of the metal-on-metal resurfacing due to multiple factors related to excessive wear rates and increased metal debris, ultimately leading to market recalls of several of these implant systems. Similarly, it is well known that implants for hemiarthroplasty that use polyethylene surfaces, instead of metal, have been associated with implant loosening due to osteolysis secondary to particulate wear. In these cases, a revision joint replacement surgery is significantly more difficult than the original surgery and is prone to complications.
Some cartilage lesions of diseased cartilage in an osteoarthritic joint can be treated with existing cartilage repair strategies. These existing surgical “repair” strategies can generally be divided into three categories: marrow stimulation, osteochondral transfer, and autologous chondrocyte implantation or ACI (as well as Matrix assisted ACI or MACI).
ACI, made publicly available in 1995, is currently the only cell-based repair procedure for articular cartilage available for clinical use in the United States. This procedure involves isolation and amplification of the patient's own chondrocytes, followed by re-implantation of cells into the cartilage defect, which is then covered by a flap of the patient's own periosteal tissue. Although clinical outcomes have been reported as good to excellent, several complications, such as graft overgrowth and the presence of loose bodies, have been reported in a significant number of patients. A number of these problems are arguably related to the lack of a scaffolding biomaterial, which would help retain cells at the site of implantation, guide and constrain the growth of the tissue, promote integration with the host cartilage, and provide the biological signals (whether endogenous or therapeutically-embedded) required for proper growth and differentiation. Unfortunately, one consistent exclusion criteria, which prevents patients from being eligible for existing cartilage repair strategies, is diffuse osteoarthritis or large areas of diseased cartilage. Accordingly, there may be defined windows of time, in which current strategies may be utilized to treat acute cartilage pathology to inhibit altogether or delay the progression to osteoarthritis.
A brief review of relevant literature indicates successful clinical results for these three broad categories of cartilage repair, albeit with overarching caveats, namely: (1) no diffuse osteoarthritis; (2) no concomitant instability; (3) patients should be younger than 45 years old; and (4) the lesions should be smaller than 4 cm2.
In an attempt to expand the use of existing cartilage repair techniques, there have been several studies undertaken to treat osteoarthritis in this young patient population. Osteochondral transfer, along with microfracture procedures have been attempted with larger lesions, and have clearly demonstrated inferior results relative to the treatment of smaller, contained lesions. Recent efforts have also involved extending the inclusion criteria of the second generation ACI or MACI procedure in order to treat chronic disease in young patients. A high failure rate of 27.3% has been reported in young patients treated with the MACI procedure after a 9-year mean follow-up. Similarly, poor results and a large percentage of failure have been reported in young patients treated with the ACI technique in osteoarthritis situations. Taken together, these results suggest a demanding joint environment for tissue engineering strategies and a need for materials with appropriate mechanical properties to not only survive in the joint but also to support and promote a regenerative response for long-term functionality.
Because of the unmet clinical need to repair and regenerate articular cartilage, there continues to be a significant interest in improved tissue engineering strategies for this purpose. This interest has escalated in the last 15 years, resulting in more than 20 cartilage tissue engineering products focused on focal defect repair that are in various stages of development or approval. These products focus largely on the use of biomaterials that improve upon methods to trap cells within a defect. Others have focused on creating bilayer osteochondral implants to recreate the bilayer structure of osteochondral tissue, but are not able to replicate the mechanical properties of the native tissues.
Relevant literature is replete with other approaches to grow functional tissues in vitro, which have been and are currently being explored in the research setting, using both synthetic and natural polymeric materials. Such approaches include using fibrous meshes and foams made of biodegradable β-hydroxy esters (e.g., polyglycolic acid and polylactic acid), peptide-modified polymers, collagen, hyaluronic acid, and chitosan, along with macroporous hydrogels of agarose and alginate. Such scaffold designs have been generally successful in forming structures histologically similar to cartilage. It has proven more difficult, however, to effectively recreate both the biomechanical and biochemical function of the natural tissue, particularly at early times after implantation. For example, the initial (i.e., post-culture, pre-implantation) mechanical properties of biodegradable polymer constructs have tended to be too stiff, while conversely, seeded hydrogels at the same stage have displayed insufficient stiffness, especially in tension, which is required to enable fluid pressurization and load support. It has been suggested that an idealized scaffold should be stiff enough to withstand the expected in vivo loading while allowing, and even promoting, the biosynthesis of functional tissue within the scaffold. Because currently existing products do not replicate the functional properties of the native tissues, they can only be used for small lesions, not large, degenerated cartilage surfaces.
U.S. Pat. No. 8,691,542 discloses a three-dimensional woven scaffold for cartilage tissue resurfacing. The three-dimensional woven scaffold is used to resurface a number of defects in the cartilage surface by replacing the articular cartilage surface. However, the three-dimensional scaffold in the '542 patent does not employ an anchoring means, and does not incorporate a shape maintaining and anchoring layer.
Other references have disclosed the use of multiphasic materials for the use of osteochondral tissue engineering. U.S. Pat. Nos. 7,776,100 and 7,963,997 disclose a cartilage region comprising a polyelectrolytic complex joined with a subchondral region with a hydrophobic barrier between the regions, wherein the polyelectrolytic complex transforms to a hydrogel. U.S. Pat. No. 6,319,712 discloses a biohybrid articular surface replacement in the form of a three-dimensional, porous carrier for cell growth and tissue development with a separate agent for aiding in osseous integration.
U.S. Pat. No. 6,306,169 discloses a biomechanical implant that is composed of two matrix components: the first component composed of a collagen, and the second component composed of a hydrated alginate for use in damaged cartilage tissue. U.S. Pat. No. 5,607,474 discloses a carrier for supporting replenished tissue growing in a diseased or damage system of a region of tissue having different mechanical properties. This patent discloses two porous layers that are amenable to tissue growth of the two different layers of tissue with corresponding mechanical properties of the two disparate tissue layers. U.S. Pat. No. 7,217,294 discloses the use of a two or three dimensional biodegradable scaffold implanted in the osteochondral lesion below one or more layers of sealants, wherein the sealants separate the layers of bone and cartilage.
U.S. Pat. No. 5,842,477 discloses the implantation of a three-dimensional scaffold structure in combination with periosteal or perichondrial tissue for the purposes of cartilage repair. U.S. Pat. No. 9,072,815 discloses a multilayered collagen scaffold suitable for osteochondral tissue repair comprising a first layer of type I collagen and hyaluronic acid, a second layer comprising a mixture of type I and II collagen and hyaluronic acid and a third layer of type I and type II collagen and another polymer or biologic (e.g., glycosaminoglycan).
U.S. Pat. No. 8,685,107 discloses a double-structured tissue implant comprising a primary scaffold with a plurality of pores and a secondary cross-linked collagenous scaffold within said pore structure for the repair of cartilage defects. This is a single-phase (i.e., one structure consisting of the combination of two materials) composite material for the purposes of cartilage repair and thus seeks the restoration of the cartilage layer upon implantation. Similarly, U.S. Pat. Nos. 8,192,759, 8,444,968, 8,512,730, and 8,580,289 disclose a single phase implant for osteochondral (as well as using the same material for other tissues) repair with a matrix comprising a polyester polymer entangled with a polysaccharide polymer.
U.S. Pat. No. 5,736,372 discloses cells mixed with a biocompatible matrix consisting of polymer fibers, incubated in vitro, and then implanted into the cartilage defect to ultimately form a cartilaginous structure in vitro. This is also a single-phase mixture for articular cartilage repair.
U.S. Pat. No. 8,226,715 discloses a plurality of three-dimensional woven bioresorbable fibers for the purposes of tendon and ligament reconstruction. The woven structure is one method of anchoring the tendon/ligament repair device into the bone in which the three-dimensional woven construct is not intended to incorporate into bone but rather relies on the rigid, porous, shape-maintaining structure to which the three-dimensional woven layer is bonded.
The aforementioned patents disclose methods and implants for treating cartilage defects, and many rely on at least two different components in a layered approach (biphasic or triphasic) to repair the osteochondral lesion (i.e., bone and cartilage). The prior art does not contain an ordered, woven matrix and does not provide anchoring, shape-maintaining features.